Soft, supple and flexible skin has a marked cosmetic appeal and is an attribute of normal functioning epidermis. As human skin ages with advancing years, the epidermis can become folded, ridged or furrowed to form wrinkles. These signal loss of youthful appearance and herald the transition to old age. Exposure to excessive doses of sunlight accelerates the transition process. The outer layer of the epidermis (the stratum corneum) can also become dry and flaky following exposure to cold weather or excessive contact with detergents or solvents. Loss of skin moisture thereby results, and the skin begins to lose the soft, supple and flexible characteristics.
These aging and dry effects on the skin can be a source of irritation, pain and great concern for patients. The use of over the counter creams or lotions to treat fine lines and wrinkles, and act as an anti-aging skin conditioner is prevalent in our society. It is estimated that over fifty percent (50%) of women over age 50 use a skin cream or lotion to improve their complexion.
In addition to the aging and drying effects on the skin, skin conditions such as rosacea affect about 10% of the United States population, and there are estimated to be over 45 million sufferers of rosacea worldwide according to the Rosacea Research & Development Institute. Rosacea is a chronic and progressive disorder of the face, characterized by some or all of the following symptoms: extremely sensitive skin, blushing, flushing, permanent redness, burning, stinging, swelling, papules, pustules, broken red capillary veins, red gritty eyes (which can lead to visual disturbances) and in more advanced cases, a disfiguring bulbous nose. There exists a need for more and better types of topical skin compositions for this skin condition, and other skin conditions such as mild eczema and psoriasis.
There are several types of non-prescription (or “over the counter”) topical skin compositions to moisturize the skins. While there are several products that moisturize the skin, their effectiveness on conditions such as rosacea, fine lines and wrinkles, mild eczema and psoriasis, and as an anti-aging skin conditioner may be less than acceptable for many patients. There is a need for improved skin compositions for patients where it is not necessary or desirable for the inclusion of a compound that would require a prescription.
An example of a non-prescription skin lotion that provides benefits and advantages in several skin condition areas is CeraVe®, brand of skin lotion, the trademark is registered to Healthpoint, Ltd. DFB Pharmaceuticals, Inc., San Antonio, Tex. CeraVe® brand of skin lotion uses a multivesicular emulsion skin care delivery system formulation described and claimed in U.S. Pat. No. 6,709,663 entitled Multivesicular Emulsion Drug Delivery Systems, to Robert Espinoza, and assigned to Healthpoint, Ltd. The phrase “multivesicular emulsion delivery system” or “multivesicular emulsion skin care delivery system” as used herein and through this patent disclosure refers to a topical skin delivery composition as has been described and claimed in detail in U.S. Pat. No. 6,709,663. The applicant incorporates by reference herein the entire content of U.S. Pat. No. 6,709,663 as though repeated herein.
An example of another non-prescription skin lotion, different than the multivesicular emulsion skin care delivery system in CeraVe® skin lotion, would be a skin lotion that uses a micelle structure delivery system for nourishing layers of the skin. The following is a description of a micelle structure from Wikipedia.org, the free on-line encyclopedia, at http://en.wikipedia.org/wiki/Micelle:
A micelle (rarely micella, plural micellae) is an aggregate of surfactant molecules dispersed in a liquid colloid. A typical micelle in aqueous solution forms an aggregate with the hydrophilic “head” regions in contact with surrounding solvent, sequestering the hydrophobic tail regions in the micelle centre. This type of micelle is know as a normal phase micelle (oil-in-water micelle). Inverse micelles have the headgroups at the centre with the tails extending out (water-in-oil micelle). Micelles are approximately spherical in shape. Other phases, including shapes such as ellipsoids, cylinders, and bilayers are also possible. The shape and size of a micelle is a function of the molecular geometry of its surfactant molecules and solution conditions such as surfactant concentration, temperature, pH, and ionic strength. The process of forming micellae is known as micellisation and forms part of the phase behavior of many lipids according to their polymorphism.
The ability of a soapy solution to act as a detergent has been recognized for centuries. However it was only at the beginning of the twentieth century that the constitution of such solutions was scientifically studied. Pioneering work in this area was carried out by James William McBain at the University of Bristol. As early as 1913 he postulated the existence of “colloidal ions” to explain the good electrolytic conductivity of sodium palmitate solutions, [McBain, J. W., Trans. Faraday Soc. 1913, 9, 99.] These highly mobile, spontaneously formed clusters came to be called micelles, a term borrowed from biology and popularized by G. S. Hartley in his classic book “Paraffin Chain Salts, A Study in Micelle Formation”. [Hartley, G. S., Aqueous Solutions of Paraffin Chain Salts, A Study in Micelle Formation, 1936, Hermann et Cie, Paris.]
Solvation
Individual surfactant molecules that are in the system but are not part of a micelle are called “monomers.” In water, the hydrophilic “heads” of surfactant molecules are always in contact with the solvent, regardless of whether the surfactants exist as monomers or as part of a micelle. However, the lipophilic “tails” of surfactant molecules have less contact with water when they are part of a micelle—this being the basis for the energetic drive for micelle formation. In a micelle, the hydrophobic tails of several surfactant molecules assemble into an oil-like core the most stable form of which has no contact with water. By contrast, surfactant monomers are surrounded by water molecules that create a “cage” of molecules connected by hydrogen bonds. This water cage is similar to a clathrate and has an ice-like crystal structure.
Micelles composed of ionic surfactants have an electrostatic attraction to the ions that surround them in solution, the latter known as counterions. Although the closest counterions partially mask a charged micelle (by up to 90%), the effects of micelle charge affect the structure of the surrounding solvent at appreciable distances from the micelle. Ionic micelles influence many properties of the mixture, including its electrical conductivity. Adding salts to a colloid containing micelles can decrease the strength of electrostatic interactions and lead to the formation of larger ionic micelles. This is more accurately seen from the point of view of an effective change in hydration of the system.
Energy of Formation
Micelles only form when the concentration of surfactant is greater than the critical micelle concentration (CMC), and the temperature of the system is greater than the critical micelle temperature, or Krafft temperature. The formation of micelles can be understood using thermodynamics: micelles can form spontaneously because of a balance between entropy and enthalpy. In water, the hydrophobic effect is the driving force for micelle formation, despite the fact that assembling surfactant molecules together reduces their entropy. Broadly speaking, above the CMC, the entropic penalty of assembling the surfactant molecules is less than the entropic penalty of caging water molecules. Also important are enthalpic considerations, such as the electrostatic interactions that occur between the charged parts surfactants.
Inverse Micelles
In a non-polar solvent, it is the exposure of the hydrophilic head groups to the surrounding solvent that is energetically unfavorable, giving rise to a water-in-oil system. In this case the hydrophilic groups are sequestered in the micelle core and the hydrophobic groups extend away from the centre. These inverse micelles are proportionally less likely to form on increasing headgroup charge, since hydrophilic sequestration would create highly unfavorable electrostatic interactions.
Uses
When surfactants are present above the CMC (Critical micelle concentration), they can act as emulsifiers that will allow a compound normally insoluble (in the solvent being used) to dissolve. This occurs because the insoluble species can be incorporated into the micelle core, which is itself solubilized in the bulk solvent by virtue of the head groups' favorable interactions with solvent species. The most common example of this phenomenon is detergents, which clean poorly soluble lipophilic material (such as oils and waxes) that cannot be removed by water alone. Detergents also clean by lowering the surface tension of water, making it easier to remove material from a surface. The emulsifying property of surfactants is also the basis for emulsion polymerization.
Micelle formation is essential for the absorption of fat-soluble vitamins and complicated lipids within the human body. Bile salts formed in the liver and secreted by the gall bladder allow micelles of fatty acids to form. This allows the absorption of complicated lipids (e.g., lecithin) and lipid soluble vitamins (A, D, E and K) by the small intestine within the micelle.
There is a need for an improved skin care composition, such as a skin lotion, that does not need to be available by prescription, and improves upon the benefits of the skin lotion, such as CeraVe® brand of skin lotion, and is well tolerated and accepted by patients as an effective treatment for dry skin, rosacea, fine lines and wrinkles, mild eczema and psoriasis, and as an anti-aging skin conditioner.